Cardiovascular effects of centrally administered endothelin-1 in rats

The effect of centrally administered endothelin-1 (ET-1) or IRL 1620 (5, 15, and 45 ng) on systemic hemodynamics was studied in anesthetized rats using a radioactive microsphere technique. Administration of saline (5 microliters, i.c.v.) did not product any significant cardiovascular effects. The lower doses of ET-1 (5 and 15 ng) did not produce any significant effect on blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR). However, the highest dose (45 ng) produced a transient rise followed by a sustained fall in BP. The CO and SV decreased significantly, whereas HR and TPR were not affected. Pretreatment with BQ-123 (10 micrograms, i.c.v.) 15 min before administration of ET-1, completely antagonized the systemic hemodynamic effects of ET-1. Centrally administered IRL 1620, a specific ETB receptor agonist, did not produce any effect on BP, HR, CO, SV, and TPR in rats. It is concluded that ETA but not ETB receptors are involved in the central cardiovascular actions of ET.